Banerjee Bhaskar, Shaheen Nicholas J, Martinez Jessica A, Hsu Chiu-Hsieh, Trowers Eugene, Gibson Blake A, Della'Zanna Gary, Richmond Ellen, Chow H-H Sherry
College of Medicine, University of Arizona, Tucson, Arizona.
Division of Gastroenterology & Hepatology, School of Medicine, University of North Carolina, Chapel Hill, North Carolina.
Cancer Prev Res (Phila). 2016 Jul;9(7):528-33. doi: 10.1158/1940-6207.CAPR-15-0276. Epub 2016 Feb 23.
Prior research strongly implicates gastric acid and bile acids, two major components of the gastroesophageal refluxate, in the development of Barrett's esophagus and its pathogenesis. Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, has been shown to protect esophageal cells against oxidative stress induced by cytotoxic bile acids. We conducted a pilot clinical study to evaluate the clinical activity of UDCA in patients with Barrett's esophagus. Twenty-nine patients with Barrett's esophagus received UDCA treatment at a daily dose of 13 to 15 mg/kg/day for 6 months. The clinical activity of UDCA was assessed by evaluating changes in gastric bile acid composition and markers of oxidative DNA damage (8-hydroxydeoxyguanosine), cell proliferation (Ki67), and apoptosis (cleaved caspase-3) in Barrett's esophagus epithelium. The bile acid concentrations in gastric fluid were measured by liquid chromatography/mass spectrometry. At baseline, UDCA (sum of unchanged and glycine/taurine conjugates) accounted for 18.2% of total gastric bile acids. After UDCA intervention, UDCA increased significantly to account for 93.4% of total gastric bile acids (P < 0.0001). The expression of markers of oxidative DNA damage, cell proliferation, and apoptosis was assessed in the Barrett's esophagus biopsies by IHC. The selected tissue biomarkers were unchanged after 6 months of UDCA intervention. We conclude that high-dose UDCA supplementation for 6 months resulted in favorable changes in gastric bile acid composition but did not modulate selected markers of oxidative DNA damage, cell proliferation, and apoptosis in the Barrett's esophagus epithelium. Cancer Prev Res; 9(7); 528-33. ©2016 AACRSee related article by Brian J. Reid, p. 512.
先前的研究有力地表明，胃食管反流物的两种主要成分——胃酸和胆汁酸，与巴雷特食管的发生及其发病机制有关。熊去氧胆酸（UDCA）是一种亲水性胆汁酸，已被证明可保护食管细胞免受细胞毒性胆汁酸诱导的氧化应激。我们进行了一项初步临床研究，以评估UDCA对巴雷特食管患者的临床疗效。29例巴雷特食管患者接受UDCA治疗，每日剂量为13至15 mg/kg/天，持续6个月。通过评估巴雷特食管上皮中胃胆汁酸成分的变化以及氧化DNA损伤标志物（8-羟基脱氧鸟苷）、细胞增殖标志物（Ki67）和细胞凋亡标志物（裂解的半胱天冬酶-3）来评估UDCA的临床疗效。通过液相色谱/质谱法测量胃液中的胆汁酸浓度。在基线时，UDCA（未改变的以及甘氨酸/牛磺酸共轭物的总和）占总胃胆汁酸的18.2%。UDCA干预后，UDCA显著增加，占总胃胆汁酸的93.4%（P < 0.0001）。通过免疫组化评估巴雷特食管活检组织中氧化DNA损伤、细胞增殖和细胞凋亡标志物的表达。UDCA干预6个月后，所选组织生物标志物未发生变化。我们得出结论，高剂量补充UDCA 6个月可使胃胆汁酸成分发生有益变化，但并未调节巴雷特食管上皮中氧化DNA损伤、细胞增殖和细胞凋亡的所选标志物。《癌症预防研究》；9(7)；528 - 33。©2016美国癌症研究协会。见Brian J. Reid的相关文章，第512页。
